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channels, one cannot distinguish easily between disordered water molecules that make up the solution, and ordered ones that are an integral part of a large biomolecular complex. Computation is usually needed to perform such distinction, for example by molecular dynamics simulations. The first part of this colloquium illustrates a study of the M2 proton channel from the influenza A virus: M2 is a tetrameric bundle of alpha-helices, whose central pore is blocked most efficiently by aklyl-ammonium molecules. Confined water clusters impose significant constraints on the molecular design of the inhibitors, by dictating both the position of the ammonium ion and the size and shape of the hydrophobic scaffold. The second part illustrates a simulation study of the multilamellar lipid matrix of the stratum corneum, the outer layer of mammalian skin. The disparity in the molecular lengths of the skin's lipids creates a coexistence of different spacings in the multilamellar structure. Water molecules amplify these differences by coalescing into nanometer-size droplets, analogous to the larger lacunar spaces that can be observed by cryo-microscopy. The interfacial tension between water and lipids governs the equilibrium structure over a wide range of humidity and pH, as shown by a direct calculation of the configurational entropy. This model can be used to predict the permeation of harmful chemicals, or as a basis to design simpler delivery systems for current medications.

See
http://dx.doi.org/10.1126/science.1197748
for a perspective on the structures of the M2 viral protein
and
http://dx.doi.org/10.1021/ja204969m
for a report on designed drugs against it.

An article targeted for non-scientists can be found at
https://www.olcf.ornl.gov/2014/08/25/oak-ridge-supercomputer-turns-the-tide-for-consumer-products-research/